Abstract

Synchronous malignancy with squamous cell carcinoma (SCC) in the head and neck
occurs mainly in the aerodigestive tract, with a frequency of 60-70%. In contrast, SCC in the
head and neck very rarely coincides with malignant lymphoma (ML). Here we report a case
of synchronous SCC on the lower-left surface of the tongue and ML on the left –side of the
neck in a 75-year-old man. The patient had consulted a local doctor for a mass on the left side
of his neck. After enucleation of the neck mass, the pathological diagnosis was metastatic
malignant tumor of unspecified origin. On the other hand, the tongue lesion was regarded as
benign and followed-up. For further diagnosis of the lesions, the patient was transferred to
our hospital in March 2015. Biopsy indicated tongue SCC. Resection of the primary tongue
lesion and radical neck dissection of the left side neck were then performed. The cervical
mass was diagnosed as ML, and found to be simultaneously affected by the tongue SCC and
cervical ML. Approximately two years later, a follow-up CT showed recurrent ML on the left
tonsil, which was treated by chemotherapy.

Keywords

Introduction

The incidence rate of synchronous carcinoma is approximately 11.0 ～ 16.2% [1]. The
second primary malignancy in patients with head and neck carcinomas is usually located
in the head and neck region (40%), lung (31%), or esophagus (9%) [2]. However, the
simultaneous occurrence of tongue squamous cell carcinoma (SCC) and B cell lymphoma
in the neck is extremely rare. To our knowledge, only three cases of synchronous cancer
involving SCC of the tongue and cervical ML are reported in the English literature, and in
those reports, the SCC lesion was on the base of the tongue [3,4]. Furthermore, double
cancer involving SCC on the body of the tongue and jugular ML is thought to be very rare.
Here, we report a case of synchronous malignancy consisting of SCC located on the body of
the tongue and B-cell lymphoma presenting as a neck mass.

Case Presentation

A 75-year-old man who was fully active became aware of pain on his tongue and a
painless mass on the left side of his neck in January 2015. At the initial hospital, a white
lesion on the lower-left surface of the tongue was regarded as benign and subjected to followup
observation, whereas an operation of the cervical mass led to a pathological diagnosis
of metastatic malignant tumor of unspecified origin. To determine the relationship, if any,
between the white lesion of the tongue and the metastatic tumor in the neck, and for further
treatment, the patient was admitted to our hospital in March 2015.

Extraoral examination revealed an elastic soft and mobile mass without tenderness
on the left side of the cervical region, the size of a thumb tip, based on palpation (Figure
1a). Intraoral examination revealed a white lesion, not surrounded by in duration, on the
lower left surface of the tongue, 21 mm × 15 mm in size (Figure 1b). We then performed a
biopsy of the tongue lesion. The pathological diagnosis of this lesion indicated tongue SCC,
based on the presence of multiple proliferating deformed and acidophilic heterocysts, with
parakeratinized stratified squamous epithelium, intercellular bridges, and keratin pearls
(Figure 2).

Figure 1: Clinical examination.
(a) Extraoral view showing a slightly elevated mass near the left cervix.
(b) Intraoral view revealing a regularly white lesion on the left lower surface of the tongue.

Contrast-enhanced magnetic resonance imaging (contrast-enhanced MRI) and 18F-Fluoro-deoxy-glucose positron emission tomography (FDG-PET/
CT) scans were performed. Contrast-enhanced MRI (T1-weighted
images) revealed a lesion on the tongue measuring about 12 mm ×
12 mm with a depth of almost 2 mm, indicating poor invasion. The
tongue lesion was slightly enhanced in the T1-weighted images after
gadolinium administration (Figure 3a). The scans also showed an
approximately 30 mm × 25 mm mass in the back-left region of the
submandibular gland (Figure 3b). No swelling was observed in the
other lymph nodes. The FDG-PET/CT scan also detected a region
of sharply enhanced FDG uptake (SUV max=17.9) with a maximum
diameter of 23.5 mm in the left cervical field (Figure 3c). In contrast,
the tongue cancer could not be visualized by FDG-PET/CT, which is
unusual for metastatic SCC. Based on these results, we diagnosed this
case as tongue SCC T1N2bM0 by UICC/AJCC staging.

Figure 3: Contrast-enhanced axial T1-weighted MR.
(a) The tongue lesion was approximately 12mm×12mm, and its depth was almost 2mm.
(b) MR image of the neck revealing an approximately 30 mm × 25 mm mass.
(c) FDG-PET/CT image showing an FDGpositive mass located in LevelⅡ

Therefore, we considered the possibility of tongue SCC with
metastatic lymph nodes. In April 2015, under general anesthesia, a
partial glossectomy and modified radical neck dissection (mRND)
were performed. The tongue specimen did not include residual
SCC. This may be the reason why the SCC had already been removed
from the tongue when we performed biopsy of the tongue lesion.
The pathological examination revealed that the cervical lymph
node did not include malignant tumor cells derived from the tongue
lesion, but had features of B-cell lymphoma (Figures 4a,4b). An immunophenotypic study of the neck specimen, classified it as B-cell
lymphoma (Figures 5a,5b,5c). Immunohistochemistry showed that
the tumor was positive for CD20, bcl-2, Ki-67, CD79a, and CD21,
and negative for CD3, CD5, CD30, CD10, cyclinD1, and bcl-6. Due
to inadequate fixation of the specimen, categorization of the B-cell
lymphoma was difficult, although follicular lymphoma was suspected
as the most likely diagnosis.

Figure 4: Photomicrograph of the mass in the left side of the neck.
(a) Low-power view revealing the histology of some sort of B-cell lymphoma.
(b) Higher magnification showing irregular nodular and proliferating atypical lymphocytes of small to moderate size.

The stage of the B-cell lymphoma was Ann Arbor. Thus, the
diagnosis was synchronous carcinoma with tongue SCC and B-cell
lymphoma.

The patient was subsequently followed up for signs of recurrence
in the left cervix and metastases of the tongue by the Hematology
department and our department. In September 2017, although
recurrence of the tongue cancer has not been detected, malignant
lymphoma in the palatine tonsilla was detected by follow-up CT scans,
and the patient is receiving chemotherapy with R-Bendamustine
once a month.

Discussion

In cancer of the oral region, it is not unusual to encounter a case
of tongue SCC and cervical mass. In most of these cases, the neck
mass is diagnosed as a metastasis from the oral SCC. However, neck dissection can reveal unexpected findings, as in our case. Sheahan et
al. performed a retrospective review of 202 patients and concluded
that unanticipated findings are occasionally encountered during
the pathologic examination of neck dissections [5]. Specifically,
unpredicted pathologies were discovered during the neck dissection
in more than 5% of patients with head and neck carcinoma, nearly half
of which were malignant tumors [5]. In our case, the simultaneous carcinoma consisting of tongue SCC and cervical ML fits the definition
of unexpected findings and represents an unusual case.

It is well known that most second primaries in head and neck
carcinoma patients occur in the lung, head and neck, or esophagus.
Leon et al. noted that the second primary malignancy in patients with
head and neck carcinomas was predominately situated in the head and neck (40%), lung (31%), or esophagus (9%) [2]. Furthermore,
when simultaneous primaries occur in the head and neck, the
coincidence of SCC and ML appears to be very rare. Watanabe et al.
reported that simultaneous malignancies of SCC and ML in the head
and neck region are extremely uncommon; they only knew of two
cases in the literature [6]. Consistent with that study, in Sheahan
et al.’s survey of 202 consecutive patients with SCC in the head and
neck, only ten patients had unexpected findings, only one of which
was lymphoma [5]. Similarly, Young-Hoo et al reported that to their
knowledge, there were ten cases of multiple primary malignancies
with head and neck SCC and malignant lymphoma [7].

Moreover, in the co-occurrence of SCC and ML, tongue SCC with
cervical ML-like our case is thought to be extraordinarily uncommon.
Watanabe et al. reported that SCC of the skin appears to be the
most common second primary malignancy in patients with ML [6].
Moreover, Sheahan et al. reported that only one case of skin SCC with
Non-Hodgkin’s Lymphoma (NHL) was detected among 274 patients
with SCC who were retrospectively reviewed [5]. Thus, it appears
that even double cancers with skin SCC and NHL seldom occur, and
are even rarer when the SCC and ML are at other anatomic sites, for
example, tongue SCC and neck ML. Furthermore, Stack et al reported
that only 2 cases of synchronous carcinoma involving SCC on the base
of the tongue and neck ML were found among 866 patients diagnosed
with SCC from 1988 to 1993 at their institutions [3]. Similarly, a case
of double cancer involving SCC at the base of the tongue and neck
ML was deemed unusual by Millwaters et al [4]. The tongue base
is adjacent to the pharynx, and ML of the tongue base cannot be
easily distinguished from pharyngeal ML. Thus, the simultaneous
occurrence of SCC at the body of the tongue and cervical ML, as
observed in our case, appears to be extremely rare. In fact, to our best
knowledge, there are no reports of SCC on the body of the tongue
with cervical ML.

In terms of the elevated risk of Second Primary Malignancy (SPM),
it is notable that patients with head and neck SCC have a significantly
elevated risk of SPM, most commonly within the head and neck, lung,
or esophagus. Morris et al. reported that in patients with index head
and neck SCC, the risk of lung cancer was most markedly elevated,
followed by head and neck and esophageal cancer, whereas a smaller
but significant increase in the risk of lymphoma was found [8].
Furthermore, when the index SCC was in the oropharynx or larynx,
the increased risk of lymphoma was slightly elevated, but it was
not elevated when the index SCC was in the oral cavity, including
the tongue [8]. These results were based on research conducted
by the National Cancer Institute’s Surveillance, Epidemiology, and
End Results (SEER) program, the registry of which contains a total
of 75,087 cases identified between 1975 and 2006 [8]. In summary,
this population-based cohort study showed that head and neck SCC
patients have an elevated risk of SPM in the lung and bronchus, head
and neck, or esophagus, and a significantly elevated but lower risk of
SPM as lymphoma [8]. Accordingly, from the viewpoint of elevated
risk, the synchronous occurrence of tongue SCC and cervical ML, as in
our case, appears to be very rare.

ML is broadly classified into Hodgkin Lymphoma (HL) and NonHodgkin
Lymphoma (NHL), and the number of NHL cases, which
include follicular lymphoma and small cell lymphocytic lymphoma,
exceeds that of HL [3-6]. The B-cell lymphoma in our case was
categorized as NHL; in Japan, NHL is much more common than HL,
with frequencies of 90% and 7%, respectively [9].

Thus, it appears that the malignancies seen in our case (tongue
SCC and cervical ML) seldom coexist. Nevertheless, because the
coexistence of SCC and ML generally result in a poor prognosis, a
cervical mass should be carefully diagnosed to guide treatment for
the best prognosis. Gluckman and Crissman reported an overall
5-year disease survival rate of 35% for single cancer and 22.3% for
multiple primary cancers [10]. Likewise, Boddie et al. reported that
patients with reticuloendothelial malignancy and primary tumors of
the oral cavity had a very short survival time (average, 8.5 months)
[11]. Accordingly, it is important to examine a neck mass carefully as
soon as it is detected. In this respect, ultrasonography (USG) and Fine
Needle Aspiration (FNA) biopsy are useful for checking a cervical mass. According to Joshi, USG has many advantages, including being
radiation free, broadly available, simple to use, noninvasive, and
inexpensive[12]. Furthermore, according to Ying et al., the cervical
lymph nodes are commonly evaluated by CT and MRI, which are
less effective than USG for identifying small nodes [13]. Ultrasound
examination of the cervical lymph nodes should be routinely applied
by clinicians to obtain a diagnosis without delay. USG is also used to
guide FNA biopsy.

Considering that cases of double cancer have increased, when
a cervical mass is found in a clinical examination, synchronous
malignancy in the head and neck region should be suspected [14].

Conclusion

The simultaneous occurrence of tongue SCC and neck ML
appears to be a very unusual event, especially the coexistence of
SCC at the body of tongue and cervical ML, as in our case. Therefore,
considering that such cases can still exist, it is important to obtain a
precise diagnosis using USG and FNA as early as possible, to guide the
treatment plan and improve the prognosis.

References

Miyahara H. Primer of Diagnosis and Treatment for Malignant
Disease in Otolaryngology, Head and Neck Surgery: TOKYO
IGAKUSYA. 2004;61-68.